title: In vitro efficiency of the piperacillin/tazobactam combination against inhibitor-resistant TEM- and complex mutant TEM-producing clinical strains of Escherichia coli.
abstract: OBJECTIVE
  We investigated the bacteriostatic and bactericidal activities of piperacillin/tazobactam against 16 clinical Escherichia coli producing inhibitor-resistant TEM β-lactamases (IRT; 13/16) and complex mutant TEM enzymes (CMT; 3/16).
  
  
  METHODS
  Bacteriostatic activity was evaluated by three methods (disc diffusion, Vitek2 automated system, MIC determination by a microdilution method) and a time-killing study was used to investigate the bactericidal effect against standard (5 × 10(5) cfu/mL) and high inocula (5 × 10(6) cfu/mL).
  
  
  RESULTS
  Piperacillin/tazobactam was bacteriostatic against most of the tested strains (15/16). Using a high inoculum, the piperacillin/tazobactam combination was not bactericidal against the 13 IRT-producing strains and one of the CMT-producing strains (1/3). A loss of bactericidal activity was still observed for seven IRT-producing strains (7/13) with a standard bacterial inoculum (<99.9% killing over 24 h).
  
  
  CONCLUSIONS
  Despite usual in vitro bacteriostatic activity, the piperacillin/tazobactam combination was not bactericidal against most IRT-producing clinical strains of E. coli, especially for the treatment of a high bacterial inoculum. This possible loss of bactericidal effect should be brought to the attention of physicians and may require high dosing regimens for the treatment of severe infections.
authors.affiliation: CHU Clermont-Ferrand, Centre de Biologie, Laboratoire de bactériologie clinique, Clermont-Ferrand, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Robin
authors.forename: Marion
authors.initials: M
authors.lastname: Krebs
authors.forename: Julien
authors.initials: J
authors.lastname: Delmas
authors.forename: Lucie
authors.initials: L
authors.lastname: Gibold
authors.forename: Caroline
authors.initials: C
authors.lastname: Mirande
authors.forename: Richard
authors.initials: R
authors.lastname: Bonnet
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D004926:Escherichia coli / Q000187:drug effects* / Q000201:enzymology* / Q000254:growth & development / Q000302:isolation & purification; D004927:Escherichia coli Infections / Q000382:microbiology; D029968:Escherichia coli Proteins / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability / Q000187:drug effects; D050505:Mutant Proteins / Q000096:biosynthesis / Q000235:genetics; D010397:Penicillanic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D010878:Piperacillin / Q000494:pharmacology; D000077725:Piperacillin, Tazobactam Drug Combination; D001618:beta-Lactamases / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D000900:Anti-Bacterial Agents; D029968:Escherichia coli Proteins; D050505:Mutant Proteins; D000077725:Piperacillin, Tazobactam Drug Combination; D010397:Penicillanic Acid; D001618:beta-Lactamases; D010878:Piperacillin